ABSTRACT
Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events.
Subject(s)
Apoptosis , Mitochondria, Muscle/metabolism , Mitochondrial Diseases/metabolism , Mitochondrial Dynamics , Muscle Fibers, Skeletal/metabolism , Nitric Oxide/biosynthesis , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Mitochondria, Muscle/genetics , Mitochondria, Muscle/pathology , Mitochondrial Diseases/genetics , Mitochondrial Diseases/pathology , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Muscle Fibers, Skeletal/pathology , Muscle Proteins/genetics , Muscle Proteins/metabolism , Nitric Oxide/genetics , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolismABSTRACT
Nitric oxide (NO) has been implicated in several cellular processes as a signaling molecule and also as a source of reactive nitrogen species (RNS). NO is produced by three isoenzymes called nitric oxide synthases (NOS), all present in skeletal muscle. While neuronal NOS (nNOS) and endothelial NOS (eNOS) are isoforms constitutively expressed, inducible NOS (iNOS) is mainly expressed during inflammatory responses. Recent studies have demonstrated that NO is also involved in the mitochondrial biogenesis pathway, having PGC-1α as the main signaling molecule. Increased NO synthesis has been demonstrated in the sarcolemma of skeletal muscle fiber and NO can also reversibly inhibit cytochrome c oxidase (Complex IV of the respiratory chain). Investigation on cultured skeletal myotubes treated with NO donors, NO precursors or NOS inhibitors have also showed a bimodal effect of NO that depends on the concentration used. The present review will discuss the new insights on NO roles on mitochondrial biogenesis and function in skeletal muscle. We will also focus on potential therapeutic strategies based on NO precursors or analogs to treat patients with myopathies and mitochondrial deficiency.
Subject(s)
Mitochondria, Muscle/metabolism , Mitochondrial Turnover/physiology , Muscle, Skeletal/metabolism , Nitric Oxide/metabolism , Animals , Electron Transport Complex IV/metabolism , Humans , Muscle, Skeletal/cytology , Nitric Oxide Synthase/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Transcription Factors/metabolismABSTRACT
A avaliação da função pulmonar em cães pode ser obtida mediante exames cintilográficos, os quais incluem a injeção de radiofármacos, seguida de radiografias. Neste estudo, foram utilizados 10 cães machos hígidos da raça Rottweiler e radiograficamente normais e soronegativos para dirofilariose, com administração de doses variadas de macroagregado de albumina sérica humana marcados com tecnécio-99m ([99mTc](MAA)). Os resultados foram avaliados qualitativa e quantitativamente, considerando o índice de perfusão pulmonar e sua homogeneidade, sendo dessa maneira visualizado um aumento na homogeneidade da imagem diretamente relacionado ao número de partículas de MAA injetado. Este estudo define os critérios de normalidade e de dosagem na perfusão pulmonar em cães hígidos da raça Rottweiller estabelecidos com a técnica de cintilografia.
Pulmonary function evaluation in dogs can be gotten by scintigraphy exams, which are obtained with radiopharmacs injections, followed by radiography. In this study it was used 10 healthful male dogs of Rottweiler breed, radiographically normal and serum negative for dirofilariasis, with administration of varied doses of human serum albumin grouped marked with technetium-99m (MAA). The results were evaluated qualitatively and quantitatively, considering the index of pulmonary perfusion and its homogeneity, being found an increase on the homogeneity of image directly related with the number of MAA particles injected. This study defines the criteria of normality and the dosage of pulmonary perfusion in healthful dogs established with scintigraphy technique.
